Method for inhibiting mineralization of natural tissue during implantation

Abstract

Natural tissues fixed with a tanning solution such as glutaraldehyde and intended for implantation in humans, e.g., porcine heart valve prosthetic devices, are treated with a solution of a water soluble quaternary ammonium salt such as dodecyltrimethylammonium chloride to inhibit mineralizaton, particularly calcification, of the tissue after implantation.

What is claimed is: 
     
       1. A method for inhibiting the mineralization of fixed natural tissue after implantation in a living body comprising contacting fixed natural tissue intended for implantation with an aqueous solution of a water soluble quaternary ammonium salt whose nitrogen atom has at least one alkyl group containing from 7 to 15 carbon atoms. 
     
     
       2. The method of claim 1 wherein the aqueous solution has a pH of from about 2.0 to about 10.0. 
     
     
       3. The method of claim 1 wherein the counter-ion of the quaternary ammonium salt is selected from the group consisting of chloride ion and methylsulfate ion. 
     
     
       4. The method of claim 1 wherein the substituent group is a straight chain aliphatic group. 
     
     
       5. The method of claim 1 wherein the substituent group is a branched aliphatic group. 
     
     
       6. The method of claim 1 wherein the water soluble quaternary ammonium salt is selected from the group consisting of decyltrimethylammonium chloride, dodecyltrimethylammonium chloride and myristyltrimethylammonium chloride. 
     
     
       7. The method of claim 1 wherein said natural tissue is contacted with said solution for a time sufficient to effectively inhibit future calcification of said tissue after implantation. 
     
     
       8. The method of claim 1 wherein said tissue is contacted with said solution for a period of at least 24 hours at ambient temperature. 
     
     
       9. The method of claim 1 wherein the concentration of said salt in said solution is from about 0.1 to 5% by weight. 
     
     
       10. The method of claim 1 wherein said solution comprises, in addition to said quaternary ammonium salt, up to about 1% by weight of sodium chloride, up to about 0.05% by weight each of potassium chloride, magnesium sulfate heptahydrate and dipotassium hydrogen phosphate, and up to about 0.1% by weight of sodium dihydrogen phospate. 
     
     
       11. The method of claim 1 wherein said solution comprises, in addition to said quaternary ammonium salt, about 0.8% by weight of sodium chloride, about 0.04% by weight of potassium chloride, about 0.02% by weight each of magnesium sulfate heptahydrate and dipotassium hydrogen phospate, and about 0.08% by weight of sodium dihydrogen phospate. 
     
     
       12. The method of claim 11 wherein the solution has a pH of about 7. 
     
     
       13. A method for inhibiting the calcification of fixed natural tissue after implantation in a living body which comprises contacting fixed tissue intended for implantation with a solution comprising dodecyltrimethylammmonium chloride for a time sufficient to effectively inhibit future calcification of said tissue after implantation. 
     
     
       14. The method of claim 13 wherein said solution comprises from about 0.1 to 5% by weight dodecyltrimethylammonium chloride. 
     
     
       15. The method of claim 13 wherein said tissue is contacted with said solution for a time of at least about 7 days. 
     
     
       16. The method of claim 13 wherein said solution comprises, in addition to said quaternary ammonium salt, up to about 1% by weight of sodium chloride, up to about 0.05% by weight each of potassium chloride, magnesium sulfate heptahydrate and dipotassium hydrogen phosphate, and up to about 0.1% by weight of sodium dihydrogen phosphate. 
     
     
       17. The method of claim 13 wherein said solution comprises, in addition to said quaternary ammonium salt, about 0.8% by weight of sodium chloride, about 0.04% by weight of potassium chloride, about 0.02% by weight each of magnesium sulfate heptahydrate and dipotassium hydrogen phoshpate, and about 0.08% by weight of sodium dihydrogen phosphate. 
     
     
       18. The method of claim 17 wherein the pH of said solution is about 7.0. 
     
     
       19. The method of claim 18 wherein the concentration of dodecyltrimethylammonium chloride is about 1%. 
     
     
       20. The method of claim 19 wherein the tissue is contacted with said solution of dodecyltrimethylammonium chloride for a period of about 7 days at ambient temperature. 
     
     
       21. The method of claim 13 wherein the fixed tissue is a glutaraldehyde-fixed porcine heart valve. 
     
     
       22. The method of claim 13 wherein said living body is a human.